Allelic and genotypic associations of DRD2 Taq I A polymorphism with heroin dependence in Spanish subjects: a case control study

Background: Conflicting associations with heroin dependence have been found involving the A1 allele of dopamine D2 receptor gene ( DRD2) TaqI A polymorphism. Methods: We compared two samples of unrelated Spanish individuals, all of European origin: 281 methadone-maintained heroin-dependent patients ( 207 males and 74 females) who frequently used non-opioid substances, and 145 control subjects ( 98 males and 47 females). Results: The A1-A1 genotype was detected in 7.1% of patients and 1.4% of controls ( P = 0.011, odds ratio = 5.48, 95% CI 1.26-23.78). Although the A1 allele was not associated with heroin dependence in the entire sample, the frequency of A1 allele was higher in male patients than in male controls ( 24.4% vs. 16.3%, P = 0.024, odds ratio = 1.65, 95% CI 1.07-2.57). A logistic regression analysis showed an interaction between DRD2 alleles and gender ( odds ratio = 1.77, 95% CI 1.15-2.70). Conclusion: Our results indicate that, in Spanish individuals, genotypes of the DRD2 TaqI A polymorphism contribute to variations in the risk of heroin dependence, while single alleles contribute only in males

Genomic history of the seventh pandemic of cholera in Africa.

The seventh cholera pandemic has heavily affected Africa, although the origin and continental spread of the disease remain undefined. We used genomic data from 1070 Vibrio cholerae O1 isolates, across 45 African countries and over a 49-year period, to show that past epidemics were attributable to a single expanded lineage. This lineage was introduced at least 11 times since 1970, into two main regions, West Africa and East/Southern Africa, causing epidemics that lasted up to 28 years. The last five introductions into Africa, all from Asia, involved multidrug-resistant sublineages that replaced antibiotic-susceptible sublineages after 2000. This phylogenetic framework describes the periodicity of lineage introduction and the stable routes of cholera spread, which should inform the rational design of control measures for cholera in Africa

Distancia a las Estrellas: El poder de la fotometría en astronomía

Durante milenios y desde las primeras propuestas para calcular la distancia aplicando trigonometría, como sugiriera Aristarco de Samos varios siglos antes de nuestra era, hasta el reconocimiento de las actuales "candelas" astrofísicas, un tipo especial de supernovas, los investigadores encontraron formas para determinar las distancias que separan a los objetos celestes. Uno de los propósitos de esta publicación es mostrar de qué manera es posible alcanzar a las estrellas al determinar las distancias que nos separan de ellas, analizando la potencia de la luz que detectamos en la Tierra, pero también busca el reconocimiento de aquellas personas que encontraron la forma de alcanzar este logro. La invitación es, finalmente, a que desarrollemos el "sentido del espacio"  en un Cosmos finito, pero ilimitado.Fil: Garcia, Beatriz Elena. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Instituto de Tecnología en Detección y Astropartículas. Comisión Nacional de Energía Atómica. Instituto de Tecnología en Detección y Astropartículas. Universidad Nacional de San Martín. Instituto de Tecnología en Detección y Astropartículas; ArgentinaFil: Moreno Luquero, Ricardo. Colegio Retamar; Españ

Utilidad de la Escala Multidimensional de Craving de Alcohol (EMCA) en la práctica clínica

Introducción: El craving es un síntoma central de las conductas adictivas cuya intensidad suele relacionarse con la evolución del paciente. La escala EMCA ha demostrado ser un instrumento válido y fiable para su evaluación. El objetivo es analizar la utilidad de la escala en la evaluación de la eficacia y en la mejora de la planificación del tratamiento del alcoholismo. Pacientes y método: Con una muestra de 151 pacientes con trastorno por dependencia de alcohol, se estudió la relación de la escala EMCA con la intensidad de la dependencia, la comorbilidad psiquiátrica y adictiva y con otras escalas utilizadas en la evaluación del alcoholismo. Finalmente, se evaluó la sensibilidad de la escala para detectar cambios en la evolución de los pacientes en un estudio de seguimiento a seis meses. Resultados: La EMCA discrimina entre el nivel grave de intensidad de la dependencia y los niveles moderado (p<0,001) y leve (p<0,001), así como entre pacientes con y sin comorbilidad adictiva (p=0,011). El factor �deseo de beber� de la EMCA discrimina entre pacientes con y sin comorbilidad psiquiátrica (p=0,041). La EMCA muestra una buena sensibilidad al cambio en el consumo de alcohol a lo largo del seguimiento. Conclusiones: La intensidad del craving parece estar modulada por la intensidad de la dependencia del alcohol y la comorbilidad psiquiátrica y adictiva. La EMCA ha demostrado ser sensible a los cambios en la evolución del curso de los pacientes alcohólicos, y por tanto, ser útil en la planificación y la evaluación de los resultados del tratamiento del alcoholismo

Allelic and genotypic associations of <it>DRD2 Taq</it>I A polymorphism with heroin dependence in Spanish subjects: a case control study

Abstract Background Conflicting associations with heroin dependence have been found involving the A1 allele of dopamine D2 receptor gene (DRD2) TaqI A polymorphism. Methods We compared two samples of unrelated Spanish individuals, all of European origin: 281 methadone-maintained heroin-dependent patients (207 males and 74 females) who frequently used non-opioid substances, and 145 control subjects (98 males and 47 females). Results The A1-A1 genotype was detected in 7.1% of patients and 1.4% of controls (P = 0.011, odds ratio = 5.48, 95% CI 1.26–23.78). Although the A1 allele was not associated with heroin dependence in the entire sample, the frequency of A1 allele was higher in male patients than in male controls (24.4% vs. 16.3%, P = 0.024, odds ratio = 1.65, 95% CI 1.07–2.57). A logistic regression analysis showed an interaction between DRD2 alleles and gender (odds ratio = 1.77, 95% CI 1.15–2.70). Conclusion Our results indicate that, in Spanish individuals, genotypes of the DRD2 TaqI A polymorphism contribute to variations in the risk of heroin dependence, while single alleles contribute only in males.</p

Allelic and genotypic associations of DRD2 TaqI A polymorphism with heroin dependence in Spanish subjects: a case control study

BACKGROUND: Conflicting associations with heroin dependence have been found involving the A1 allele of dopamine D2 receptor gene (DRD2) TaqI A polymorphism. METHODS: We compared two samples of unrelated Spanish individuals, all of European origin: 281 methadone-maintained heroin-dependent patients (207 males and 74 females) who frequently used non-opioid substances, and 145 control subjects (98 males and 47 females). RESULTS: The A1-A1 genotype was detected in 7.1% of patients and 1.4% of controls (P = 0.011, odds ratio = 5.48, 95% CI 1.26–23.78). Although the A1 allele was not associated with heroin dependence in the entire sample, the frequency of A1 allele was higher in male patients than in male controls (24.4% vs. 16.3%, P = 0.024, odds ratio = 1.65, 95% CI 1.07–2.57). A logistic regression analysis showed an interaction between DRD2 alleles and gender (odds ratio = 1.77, 95% CI 1.15–2.70). CONCLUSION: Our results indicate that, in Spanish individuals, genotypes of the DRD2 TaqI A polymorphism contribute to variations in the risk of heroin dependence, while single alleles contribute only in males

Allelic and genotypic associations of DRD2 Taq I A polymorphism with heroin dependence in Spanish subjects: a case control study

Background: Conflicting associations with heroin dependence have been found involving the A1 allele of dopamine D2 receptor gene ( DRD2) TaqI A polymorphism. Methods: We compared two samples of unrelated Spanish individuals, all of European origin: 281 methadone-maintained heroin-dependent patients ( 207 males and 74 females) who frequently used non-opioid substances, and 145 control subjects ( 98 males and 47 females). Results: The A1-A1 genotype was detected in 7.1% of patients and 1.4% of controls ( P = 0.011, odds ratio = 5.48, 95% CI 1.26-23.78). Although the A1 allele was not associated with heroin dependence in the entire sample, the frequency of A1 allele was higher in male patients than in male controls ( 24.4% vs. 16.3%, P = 0.024, odds ratio = 1.65, 95% CI 1.07-2.57). A logistic regression analysis showed an interaction between DRD2 alleles and gender ( odds ratio = 1.77, 95% CI 1.15-2.70). Conclusion: Our results indicate that, in Spanish individuals, genotypes of the DRD2 TaqI A polymorphism contribute to variations in the risk of heroin dependence, while single alleles contribute only in males

Pro-oxidant activity of amine-pyridine-based iron complexes efficiently kills cancer and cancer stem-like cells

Differential redox homeostasis in normal and malignant cells suggests that pro-oxidant-induced upregulation of cellular reactive oxygen species (ROS) should selectively target cancer cells without compromising the viability of untransformed cells. Consequently, a pro-oxidant deviation well-tolerated by nonmalignant cells might rapidly reach a cell-death threshold in malignant cells already at a high setpoint of constitutive oxidative stress. To test this hypothesis, we took advantage of a selected number of amine-pyridine-based Fe(II) complexes that operate as efficient and robust oxidation catalysts of organic substrates upon reaction with peroxides. Five of these Fe(II)-complexes and the corresponding aminopyridine ligands were selected to evaluate their anticancer properties. We found that the iron complexes failed to display any relevant activity, while the corresponding ligands exhibited significant antiproliferative activity. Among the ligands, none of which were hemolytic, compounds 1, 2 and 5 were cytotoxic in the low micromolar range against a panel of molecularly diverse human cancer cell lines. Importantly, the cytotoxic activity profile of some compounds remained unaltered in epithelial-to-mesenchymal (EMT)-induced stable populations of cancer stem-like cells, which acquired resistance to the well-known ROS inducer doxorubicin. Compounds 1, 2 and 5 inhibited the clonogenicity of cancer cells and induced apoptotic cell death accompanied by caspase 3/7 activation. Flow cytometry analyses indicated that ligands were strong inducers of oxidative stress, leading to a 7-fold increase in intracellular ROS levels. ROS induction was associated with their ability to bind intracellular iron and generate active coordination complexes inside of cells. In contrast, extracellular complexation of iron inhibited the activity of the ligands. Iron complexes showed a high proficiency to cleave DNA through oxidative-dependent mechanisms, suggesting a likely mechanism of cytotoxicity. In summary, we report that, upon chelation of intracellular iron, the pro-oxidant activity of amine-pyrimidine-based iron complexes efficiently kills cancer and cancer stem-like cells, thus providing functional evidence for an efficient family of redox-directed anti-cancer metallodrugs